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Kwang Yong Choi,1 Hwan Il Kim,1 Chin Kook Rhee,2 Kwang Ha Yoo,3 Yong Bum Park,4 Youlim Kim,3 So Eun Lee,5 Jung-Ae Kim,6 Yong Il Hwang1 1Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Hallym University Sacred Heart Hospital, Anyang-si, Gyeonggi-do, Republic of Korea; 2Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; 3Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Konkuk University Hospital, School of Medicine, Konkuk University, Seoul, Republic of Korea; 4Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Hallym University Kangdong Sacred Heart Hospital, Seoul, Republic of Korea; 5Respiratory, Medical Affairs, Boehringer-Ingelheim Korea, Seoul, Republic of Korea; 6Real-World Solutions, IQVIA Korea, Seoul, Republic of KoreaCorrespondence: Yong Il Hwang, Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Hallym University Sacred Heart Hospital, 22, Gwanpyeong-ro 170beon-gil, Dongan-gu, Anyang-si, Gyeonggi-do, 14068, Republic of Korea, Email hyicyk@hallym.or.kr; hyicyk@gmail.comBackground: COPD causes substantial economic burden on healthcare. Alternative treatment strategies for COPD can be associated with different costs dependent upon their relative safety and effectiveness. We compared costs and healthcare resource utilization (HCRU) associated with LAMA or LABA/ICS initiation.Methods: Using the Korean National Health Insurance Service database, we enrolled COPD patients initiating treatment with LAMA or LABA/ICS between January 2005 and April 2015. Propensity score matched individuals were compared on all-cause and COPD-related medical costs and HCRU over a three-year follow-up period.Results: A total of 2444 patients were enrolled in each treatment group. LAMA group was associated with significantly lower costs than LABA/ICS group, both in all-cause (403.08 vs 474.50 USD per patient per month [PPPM], cost ratio 1.18, 95% confidence interval [CI]=1.10– 1.26, p< 0.0001) and COPD-related (216.37 vs 267.32 USD PPPM, cost ratio 1.24, 95% CI=1.13– 1.35, p< 0.0001) medical costs. All-cause HCRU was not significantly different between groups, while COPD-related HRCU was higher in LAMA group (0.66 vs 0.60 medical visits PPPM, p< 0.0001).Conclusion: COPD patients initiating treatment with LAMA were associated with lower all-cause and COPD-related medical costs than those starting with LABA/ICS despite the similar all-cause HCRU and higher COPD-related HCRU. Initiation with LAMA is a cost-efficient option for the treatment of COPD.Keywords: chronic obstructive pulmonary disease, inhaled corticosteroids, long-acting beta-2 agonists, long-acting muscarinic receptor antagonists, medical cost

Epidemiological studies have linked fine dust pollution to depression, yet the underlying mechanisms remain unclear. Oxidative stress and endoplasmic reticulum (ER) stress are known contributors to depression, but their induction by particulate matter (PM), particularly PM2.5, in animal models has been limited. This study aimed to establish a rat model of PM2.5-induced depression-like behaviors and elucidate the underlying molecular mechanisms. Adult male Sprague–Dawley rats received daily intranasal PM2.5 for four weeks. Behavioral assessments, including the open field test (OFT), forced swim test (FST), and light-dark box (LDB) test, were conducted weekly. PM2.5-exposed rats displayed depressive-like behaviors, particularly in the FST, reflecting decreased motivation and learned helplessness. Molecular analyses indicated a specific increase in ER stress markers (CHOP, eIF2α, GRP78, and P16) and NOX4 in the hypothalamus, while other brain regions (striatum, cortex, and hippocampus) were not as pronounced. Additionally, PM2.5 exposure reduced tyrosine hydroxylase (TH) levels in the hypothalamus, suggesting impaired dopamine synthesis. These findings indicate that PM2.5 induces depressive-like behaviors via hypothalamic ER stress and oxidative stress pathways, leading to dopaminergic dysfunction. Targeting oxidative and ER stress within the hypothalamus may offer new therapeutic strategies for treating depression associated with environmental pollutants. [ABSTRACT FROM AUTHOR]

Urban air pollution, a significant environmental hazard, is linked to adverse health outcomes and increased mortality across various diseases. This study investigates the neurotoxic effects of particulate matter (PM), specifically PM2.5 and PM10, by examining their role in inducing oxidative stress and subsequent neuronal cell death. We highlight the novel finding that PM increases mitochondrial ROS production via stimulating NOX4 activity, not through its expression level in Neuro-2A cells. Additionally, PMs provoke ROS production via increasing the expression and activity of NOX2 in SH-SY5Y human neuroblastoma cells, implying differential regulation of NOX proteins. This increase in mitochondrial ROS triggers the opening of the mitochondrial permeability transition pore (mPTP), leading to apoptosis through key mediators, including caspase3, BAX, and Bcl2. Notably, the voltage-dependent anion-selective channel 1 (VDAC1) increases at 1 µg/mL of PM2.5, while PM10 triggers an increase from 10 µg/mL. At the same concentration (100 µg/mL), PM2.5 causes 1.4 times higher ROS production and 2.4 times higher NOX4 activity than PM10. The cytotoxic effects induced by PMs were alleviated by NOX inhibitors GKT137831 and Apocynin. In SH-SY5Y cells, both PM types increase ROS and NOX2 levels, leading to cell death, which Apocynin rescues. Variability in NADPH oxidase sources underscores the complexity of PM-induced neurotoxicity. Our findings highlight NOX4-driven ROS and mitochondrial dysfunction, suggesting a potential therapeutic approach for mitigating PM-induced neurotoxicity. [ABSTRACT FROM AUTHOR]

AbstractCourts are high-stakes institutions, where the influence of the use of legal technology (legaltech) may not be confined to the individuals utilizing the tools. The existing evidence is insufficient for predicting the approval of legaltech in court proceedings. We aimed to provide empirical support for utilizing the technology acceptance model by recognizing individuals’ perceptions of legaltech in court proceedings. Furthermore, we suggest possible distinctions in these perceptions between those with and without court experience, in the legal field versus others, men versus women, and younger versus older individuals. This study’s main purpose is to offer important insights into the determinants that impact the acceptability of legal technology within the Vietnamese court system. The findings were examined by applying the partial least squares structural equation modelling technique. Based on the results, the acceptance of technology in court proceedings is mostly influenced by views on its utility. Furthermore, trust is crucial and is influenced by perceived risk and expertise. It is recommended that policymakers and court administrators prioritize the enhancement of these aspects to promote the acceptance and utilization of legal technology in Vietnam’s courts, leading to more efficient and impactful judicial procedures.

INTRODUCTION DEFECTS IN THE NUCLEOCYTOPLASMIC TRANSPORT of transcription factors are implicated in diseases ranging from cancer to inflammatory illnesses, such as asthma. Chemical genetic phenotypic screens offer insight into the [...], Transcription factors of the nuclear factor k B family are the paradigm for signaling dependent nuclear translocation and are ideally suited to analysis through image-based chemical genetic screening. The authors describe combining high-content image analysis with a compound screen to identify compounds affecting either nuclear import or export. Validation in silico and in vitro determined an [EC.sub.50] for the nuclear export blocker leptomycin B of 2.4 ng/mL (4.4 nM). The method demonstrated high selectivity (Z' >0.95), speed, and robustness in a screen of a compound collection. It identified the IκB protein kinase inhibitor BAY 11 7082 as an import inhibitor, the p38 mitogen-activated protein (MAP) kinase inhibitor PD98509 as an import enhancer, and phorbol ester as an export inhibitor. The results establish a robust method for identifying compounds regulating nucleocy-toplasmic import or export and also implicate MAP kinases in nuclear import of nuclear factor k B. (Journal of Biomolecular Screening 2007:621-627) Key words: NF-κB, nucleocytoplasmic transport, signal transduction, second messenger-activated kinases, high-content screening, automation, image recognition